Wound healing is the process of re-establishment of the normal structure and function of a tissue after injury. Abnormal healing can result in increased rates of infection, scarring, altered integrity of the injured tissue, and impaired function. When the wound is a therapeutic intervention, e.g., periodontal surgery or cosmetic surgery, the beneficial effect may not be achievable when healing is impaired. An individual's ability to efficiently heal a wound depends upon the quality and quantity of their inflammatory response which can be modulated by neuroendocrine and genetic factors. The overall purpose of this research proposal is to determine the mechanisms by which psychosocial and genetic factors alter inflammatory responses required for oral wound healing. Academic examination stress has been shown to delay healing of oral wounds by 40%, but there is considerable individual variation as to the relative impact of this stressor. We hypothesize that the magnitude of the effect of stress is a function of psychosocial factors which alter the perception of stress and the perceived consequences of stress, and genetic polymorphisms that control the level of pro-inflammatory cytokine gene expression. Experimental oral wounds will be placed during examinations and nonstressed times to determine the mechanisms by which psychological and genetic factors alter inflammatory responses during healing. The following specific aims will address these hypotheses: To determine l) the mechanisms by which examination stress alters cellular recruitment and inflammatory responses during wound healing and how they are modulated by an individual's inflammatory genotype; 2) the relationship among psychosocial factors, neuroendocrine mediators, and delayed wound healing. Understanding the mechanisms of delayed healing, will help to determine those at greatest risk and to develop individualized interventions to ameliorate the effects of stress.